Photodynamic therapy (PDT) is a treatment procedure that uses a light to activate a photosensitizer (PS) to produce singlet oxygen for killing cancer cells or curing acne. Since the onset of PS toxicity can only be triggered by the irradiation of light, PDT generally is considered as a safe alternative for chemotherapy in the treatment of cancer, and does not induce side effects. A lot of evidences indicate that PDT-induced apoptosis is due to the damage of mitochondria and suggest that mitochondria are the target for PDT. Therefore, the efficacy of PS would be greatly enhanced if it can be delivered specifically to the mitochondria of cancer cells. In fact, research revealed that Pc 4 (a silicon phthalocyanine photosensitizer) can spontaneously partition to mitochondria due to its high hydrophobicity, which makes it an ideal PS for maximizing PDT efficacy. However, the clinical application of Pc 4 based PDT has not been widely accepted due to its poor water solubility and erratic tissue retention, especially in the skin which results in unwanted tissue damage upon the exposure to sunshine.
Additionally, much effort has been devoted to the development of PDT for head and neck cancers. However, PDT still has not been widely accepted due to its potential skin toxicity upon exposure to light, low efficiency as a result of low solubility and aggregation of the photosensitizer (PS). A carrier system that can fully take advantage of the benefits of PDT while minimizing its side effects is urgently needed.
Over past decades, many types of nanoparticle carriers have been developed for targeted delivery of Pc 4 to tumor by taking advantage of the leaky vascular structure in tumor tissue through so called enhanced permeability and retention (EPR) effect. Such systems include polymeric micelles, mesoporous silica nanoparticles, and gold nanoparticles, which can load hydrophobic Pc 4 through hydrophobic interaction. Although with the help of various ligand-receptor interactions most nanoparticles achieved enhanced cellular uptake of Pc 4, there was occasional disconnection between the uptake of PS and their PDT efficacy. Higher uptake of PS did not result in better cell killing, possibly due to the fact that those encapsulated Pc 4 could not effectively escape from lysosome and then transfer to mitochondria.